Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II Trial of Hippocampal Avoidance During Whole Brain Radiotherapy for Brain Metastases
Brief Summary: RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells.

PURPOSE: This phase II trial is studying how well avoiding the hippocampus during whole-brain radiation therapy works in treating patients with brain metastases.


Options:
A: INCLUSION CRITERIA:

* Histologically or cytologically confirmed non-hematopoietic malignancy within the past 5 years

  * If histologic proof of malignancy is from \> 5 years ago, then a more recent pathological confirmation is required (e.g., from systemic metastatic or brain metastasis)
  * Patients with metastasis of unknown primary tumor are permitted
* Measurable brain metastasis outside a 5-mm margin around either hippocampus on gadolinium contrast-enhanced MRI obtained within the past 30 days
* Have not been or will not be treated with stereotactic radiosurgery (SRS) or surgical resection

  * These treatment options are allowed only at relapse
* Patients who have brain metastases at initial presentation allowed and do not need to demonstrate 3 months of stable scans
* At least 1 week since open biopsy
* Karnofsky performance status 70-100%
* Fertile patients must use effective contraception
* Negative pregnancy test 2 weeks or less prior to study entry
* Patients must be English proficient, with patients who speak English as a second language eligible

EXCLUSION CRITERIA:

* Small cell lung cancer or germ cell malignancy
* Leptomeningeal metastases
* Non-small cell lung cancer-associated brain metastases with ≥ 2 organ sites of extracranial metastases
* Radiologic evidence of hydrocephalus
* Serum creatinine \> 1.4 mg/dL within 30 days prior to study entry
* Pregnant or nursing
* Contraindication to MRI imaging such as implanted metal devices or foreign bodies or severe claustrophobia
* Severe, active co-morbidity including any of the following:

  * Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
  * Transmural myocardial infarction within the past 6 months
  * Acute bacterial or fungal infection requiring intravenous antibiotics
  * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
  * Uncontrolled, clinically significant cardiac arrhythmias
* Prior radiotherapy to the brain
* Plan for chemotherapy or targeted therapies during WBRT or during the subsequent 7 days
B: Inclusion Criteria:

1. age 18 or older
2. fluent in English
3. able to provide informed consent to all procedures
4. diagnosis of a brain tumor
5. indication of lasting post-treatment cognitive deficits (e.g., from clinical presentation, prior neuropsychological assessment, and/or self-report)
6. sufficient motor and sensory functioning to complete study activities
7. availability to complete all study activities
8. for patients treated with cranial radiation, at least 3 months post-radiation

Exclusion Criteria:

(1) comorbid neurological or psychiatric disorder or other medical condition suspected to influence cognition
C: Inclusion criteria: Survivors will be included if they:

1. Have been treated with cranial or cranial-spinal radiation,
2. Are between 5 and 21 years of age at time of consent, and
3. Either declare English as their native language or have had at least two years of schooling in English at the time of their baseline assessment.
4. Have been diagnosed with a brain tumour requiring treatment with cranial or cranial-spinal radiation at least 2 years ago, is not receiving active treatment and no more than 15 years may have elapsed between treatment with cranial-spinal radiation and time of the trial. Survivors with a shunt will be included in the trial, but will need to be identified prior to study enrollment to discuss any specific considerations for imaging.
5. Meet criteria for adequate organ function requirements:

   1. Adequate renal function defined as: Creatinine clearance or radioisotope glomerular filtration rate (GFR) \> 70ml/min/1.73 m2 or serum creatinine based on age/gender as follows:

      Maximum Serum Creatinine Level (mg/dL)

      5 to \< 10 years: Male = 1; Female = 1

      10 to \< 13 years: Male = 1.2; Female = 1.2

      13 to \< 16 years: Male = 1.5; Female = 1.4

      ≥ 16 years: Male = 1.7; Female = 1.4
   2. Adequate liver function defined as:

   Total bilirubin \< 1.5 x upper limit of normal (ULN) for age, and,

   serum glutamate oxaloacetate transaminase (SGOT) (AST) or serum glutamate pyruvate transaminase (SGPT) (ALT) \< 3 x upper limit of normal (ULN) for age.
6. Females of childbearing potential must have a negative pregnancy test result and must agree to use a medically acceptable method of contraception throughout the entire study period and for 30 days after the last dose of study drug.
7. Informed consent will be obtained from the participants and/or their legal guardians by study team members authorized to consent for this study.

Exclusion criteria: Survivors will be excluded if they

1. Are receiving palliative care.
2. Are unable to participate in neuro-imaging without sedation as this is the primary outcome measure for the trial.
3. Are unable to swallow tablets.
4. Are unstable and/or insulin-dependent (Type 1) diabetic patients.
5. Have acute or chronic metabolic acidosis and/or lactic acidosis.
6. Any female patient or partner who has reached menarche and male patients who are not willing to use an effective method of contraception.
7. Patient who is pregnant or lactating and does not agree to stop breastfeeding while receiving trial treatment.
8. Have a history of renal disease or renal dysfunction e.g., as suggested by elevated serum creatinine levels (see 5.a. Inclusion criteria) or abnormal creatinine clearance.
9. Have a history of congestive heart failure requiring pharmacologic treatment.
10. Have a known hypersensitivity to metformin hydrochloride.
D: Inclusion Criteria:

* Diagnosed with glioblastoma, gliosarcoma, small cell or large cell glioblastoma, glioblastoma with oligo features, glioblastoma with primitive neuroectodermal tumor-like components (GBM-PNET) features, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma who are clinically stable and have completed radiation therapy (excluding stereotactic radiosurgery) \> 21 days and =\< 24 months prior to enrollment; NOTE: clinical stability will be defined as a stable or improved Karnofsky performance status (KPS) compared to the prior month
* \>= 6 score on the worst fatigue question of the BFI (Brief Fatigue Inventory, question 3); it is not required for the patient to complete the entire BFI to meet this criterion
* Undergone surgery (gross total or subtotal resection) or biopsy and will have been treated with concurrent radiation therapy and chemotherapy as standard of care for glioblastoma, gliosarcoma, small cell or large cell glioblastoma, glioblastoma with oligo features, glioblastoma with primitive neuroectodermal tumor-like components (GBM-PNET) features, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma patients; Note: radiation must be completed, but chemotherapy is allowed; patients who are currently using Optune device will be eligible to participate in this trial
* Negative serum pregnancy test done =\< 7 days prior to registration only for women determined to be of childbearing potential by their treating physician
* Ability to complete questionnaire(s) by themselves or with assistance
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, 2 or 3
* Provide informed written consent
* Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
* Stable dose of corticosteroid \>= 14 days prior to registration

Answer: A