Inclusion Criteria:  Age ≥ 18 years on the day of consenting to study ECOG performance status ≤ 2 and KPS ≥ 60. Life expectancy ≥ 8 weeks in the opinion of the Investigator  LM from any solid tumor malignancy (1a) or NSCLC (1b), that is either:  Newly diagnosed: As evidenced by positive CSF cytology, CTC count >3.0/3.0 mL, or unequivocal radiographic evidence of LM on contrast-enhanced MRI, or Recurrent: As evidenced by unequivocal radiographic progression on contrast-enhanced MRI, the development of newly or recurrently positive CSF cytology, or a clinically-relevant rise in CSF CTCs at the discretion of the treating Investigator. There are no restrictions on the number of recurrences. Confirmation of solid tumor malignancy (phase 1a) and NSCLC primary malignancy (phase 1b) may be made by histopathologic criteria of any primary or metastatic site. For patients that have not previously undergone internal pathology review at MSKCC, a pathology report confirming the primary malignancy is sufficient. Patients with all known mutational signatures of NSCLC (EGFR, ALK, ROS1, KRAS, etc. mutant and wildtype) are allowed to enroll (phase 1b). Patients can have concomitant parenchymal brain metastases at study entry as long as they do not require active treatment or have been previously treated. Patients with seizure disorders, stable on appropriate antiepileptic therapies, are eligible for this trial. Patients must have normal CSF flow dynamics at the clinical judgment of the treating investigator, with no obstructive hydrocephalus or ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt. Patients with isolated intracranial LM progression and stable extracranial disease may enroll on trial. If this population is receiving systemic treatment that is controlling their extracranial disease, they may remain on this regimen during study enrollment provided their LM progression occurred on this regimen.  For patients with both intracranial and extracranial disease progression at the time of study screening, necessitating change to their systemic tumor-directed therapy:  If the new systemic treatment of choice has known CNS activity at the discretion of the Principal Investigator, then they should be monitored on this new regimen for 21 days with confirmation of persistent LM (by neuraxial imaging and CSF reassessment) before enrolling on study. If the new systemic treatment of choice has no known CNS activity at the discretion of the Principal Investigator, then they may start IT-DFO concurrently with the new systemic treatment. Examples of systemic CNS-active treatments include but are not limited to: bevacizumab, temozolomide, carmustine, lomustine, etoposide, carboplatin, cisplatin, pemetrexed, doxorubicin, high-dose erlotinib, osimertinib, lorlatinib, lapatinib, tucatinib, capecitabine, dabrafenib, trametinib, vemurafenib, cobimetinib, ipilimumab, nivolumab, pembrolizumab, atezolizumab Patients must have a functioning Ommaya reservoir prior to the first IT-DFO administration or be an appropriate surgical candidate for Ommaya reservoir placement and agree to Ommaya reservoir placement as standard of care prior to the first IT-DFO administration.  Adequate bone marrow and organ function as demonstrated by:  White blood cell (WBC) count ≥ 2.5 K/mcL Absolute neutrophil count (ANC) ≥ 1.0 K/mcL Platelet count ≥ 50 K/mcL at least 7 days from last platelet transfusion Hemoglobin (Hgb) ≥ 8 g/dL Serum creatinine ≤ 1.5 times the upper limit of normal (ULN) Serum bilirubin ≤ 1.5 times the ULN; or total bilirubin ≤ 3 times the ULN with direct bilirubin within the normal range in patients with well documented Gilbert Disease Serum alanine aminotransferase (ALT) and aspartate aminotransaminase (AST) ≤ 3 times the ULN, unless known hepatic disease wherein may be ≤ 5 times the ULN is acceptable. Women of child-bearing potential and sexually active males must commit to the use of effective contraception while on study.  Exclusion Criteria:  Any CNS-directed irradiation within 7 days of first dose of IT-DFO. Patients receiving other therapy (either intrathecal or systemic) designed to treat their LM, with ongoing acceptable control of their LM. Any contraindication to gadolinium-enhanced MRI Use of any systemic iron chelators within 4 weeks of first dose Use of ascorbic acid or prochlorperazine within 2 weeks of first dose Patients are not allowed to receive whole-brain radiation therapy or craniospinal radiation therapy during study enrollment. Patients must not have any physical and/or psychiatric illness that would interfere with their compliance and ability to tolerate treatment as per the protocol. Women may not be pregnant or breastfeeding Known hypersensitivity or allergic reaction to iron chelating agents