Central nervous system disease Participant must not have a known uncontrolled malignancy of the central nervous system. EXCLUSION CRITERIA FOR SECOND-LINE THERAPY: Known or suspected brain or central nervous system metastases, irrespective of prior treatment EXCLUSION CRITERIA FOR THIRD-LINE THERAPY: Known or suspected brain or central nervous system metastases, irrespective of prior treatment Active central nervous system metastases Known central nervous system mass lesion Central nervous system metastases History of seizure disorders or unstable central nervous system metastases Known central nervous system metastases Central nervous system malignancy Metastatic disease to the central nervous system Patients with known central nervous system metastases, including lymphomatous meningitis Central nervous system metastases, including lymphomatous meningitis Without clinical signs of active central nervous system disease Known central nervous system or visceral metastases Known central nervous system malignancy. Note: Central nervous system imaging is only required in subjects with suspected central nervous system malignancy. Active central nervous system metastases and/or leptomeningeal disease Uncontrolled central nervous system metastases Patients/subjects with suspected or known central nervous system metastases unless adequately treated Patients with active visceral, central nervous system, or any bone metastases melanoma (stage IVMb or IVMc) Patient has known active central nervous system metastases. Must not have suspected or known central nervous system metastases unless adequately treated Active central nervous system malignancy Rapidly progressive, clinically unstable central nervous system hematological malignancy. Note: Central nervous system evaluation is only required in subjects with known or suspected central nervous system malignancy. Persons with uncontrolled central nervous system malignancy Active central nervous system malignancy History of central nervous system disease (e.g., seizures) unrelated to cancer unless adequately controlled by medication Active meningeal or central nervous system disease Presence of any central nervous system tumor that has not been stable for at least weeks off corticosteroids. Subjects must not have a history of neurodegenerative or central nervous system movement disorder AND (by central assessment) either: Significant co-morbid central nervous system disease, including but not limited to, multiple sclerosis Previous radiotherapy for central nervous system metastases Patients with known malignant disease of the central nervous system. Any history of disease involving the central nervous system (Part ). Known active disease involving the central nervous system (Part ). Active central nervous system tumor or metastases Active central nervous system malignancy Active central nervous system malignancy Patients may have active malignancy outside the central nervous system Known central nervous system brain metastases Active central nervous system malignancy Known central nervous system metastases Uncontrolled central nervous system metastases Central nervous system disease as evidence by clinical symptomatology Subjects with known central nervous system disease Patient must have no prior history or current clinically apparent central nervous system metastases Known central nervous system metastases or central nervous system as the only source of disease Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of central nervous system metastatic disease, have been off glucocorticoids for at least weeks, have no overt evidence of neurological deficit and are ? weeks from completion of brain irradiation. Active central nervous system disease. Known central nervous system metastases or central nervous system as the only source of disease Clinically active primary central nervous system tumors or brain metastases with the exception of subjects with glioblastoma multiform that carry ROS rearrangement Uncontrolled central nervous system metastases Participants with known central nervous system disease Has known active central nervous system metastases Known brain or central nervous system metastases or history of uncontrolled seizures. Individuals with known or suspected central nervous system metastases or individuals requiring chronic daily treatment with oral corticosteroids Subjects with active central nervous system metastases Known or suspected central nervous system metastases Have confirmed presence of central nervous system metastases Patients with known central nervous system metastases. Patients with brain metastases must have at least one site of measurable disease outside of the central nervous system Central nervous system metastases Brain metastases, meningeal tumours or other metastases in the central nervous system Current central nervous systemic disease Presence of known central nervous system or brain metastases Subjects with active cancer that has spread to the central nervous system Asymptomatic, central nervous system metastases are permitted Significant co-morbid central nervous system disease, including but not limited to, multiple sclerosis Clinical or radiographic evidence of central nervous system metastases or significant cardiovascular disease Central nervous system function defined as not severely somnolent or comatose (central cortical neurotoxicity scale < grade ) History of demyelinating disease or inflammatory disease of the central nervous system or the peripheral nervous system Patients with primary central nervous system tumors or brain metastases. Active or history of central nervous system metastases. Active central nervous system metastases (subjects should be stable and off anticonvulsants and steroids) History or clinically suspicious for cancer-related Central Nervous System disease Patient have uncontrolled brain metastases or central nervous system disease. Patients may have active malignancy outside the central nervous system Active central nervous system metastases Known central nervous system malignancy. Known central nervous system metastases Known or suspected brain or central nervous system metastases Known central nervous system metastases Central nervous system injury or severe neurological impairment Central nervous system metastases History of central nervous system hemorrhage Known presence of central nervous system metastases Central nervous system metastases Any history or signs of central nervous system metastases; In the investigator's judgment, focal neurologic deficit as a result of metastases in the brain, spine, or other central nervous system disorders. Severe central nervous system, pulmonary, or renal disease not related to the participant's cancer. Patient has no worsening central nervous system symptoms; and Known central nervous system disease (e.g., Alzheimer's disease). Patients with central nervous system disease Active central nervous system tumors or metastases Radiographic evidence of central nervous system metastases that are not well controlled with local therapy (irradiation or surgery) History or presence of known central nervous system metastases Subjects with known central nervous system metastases. Uncontrolled central nervous system metastases Central nervous system tumors are allowed Metastatic disease to the central nervous system Active MM involving the central nervous system. Active central nervous system lesions Known central nervous system metastases or central nervous system as the only source of disease Known or suspected brain or other central nervous system metastases Active central nervous system malignancy Known metastases to the central nervous system Subjects with known central nervous system disease Subject has a history of central nervous system radiotherapy that encompasses all or part of the cochlea or will receive such radiation therapy during the course of the study. MM involving the central nervous system.