Patients are ineligible if they have any currently active central nervous system (CNS) metastases; patients who have treated brain metastases (with either surgical resection or stereotactic radiosurgery [SRS]) could be eligible; patients must not have taken any steroids =< days prior to randomization for the purpose of managing their brain metastases; patients with only whole brain irradiation for treatment of CNS metastases will be ineligible Patients are ineligible if they have any currently active CNS metastases; patients who have treated brain metastases (with either surgical resection or stereotactic radiosurgery [SRS]) could be eligible to proceed; patients crossing over from dabrafenib/trametinib to nivolumab (nivo)/ipilimumab (ipi) must not have taken any steroids =< days prior to registration for the purpose of managing their brain metastases; patients with only whole brain irradiation for treatment of CNS metastases are ineligible Brain metastases No active brain metastases Patients with untreated brain metastases. Patients with treated brain metastases who are off corticosteroids for at least two weeks and who demonstrate control of brain metastases with follow-up imaging or more weeks after initial therapy are eligible. Documented history of or current brain metastases due to seizure risk Have no evidence of new or enlarging brain metastases Uncontrolled brain metastases Females who are pregnant or breastfeeding. ? Patients who have active or stable brain metastases or who have a history of brain metastases. Subjects with brain metastases Active brain metastases Some types of brain metastases Patients may not have diagnosed brain metastases Brain metastases (brain imaging is not required) Patients with uncontrolled brain metastases. Uncontrolled brain metastases Brain metastases. Brain metastases that: have no evidence of new or enlarging brain metastases, and Recurrent brain metastases Subjects with brain metastases are eligible Patients with uncontrolled brain metastases. Existing brain metastases must have been previously treated and currently stable. Patients with active brain metastases are not eligible; patients with brain metastases that have been treated and stable for > days following treatment will be eligible Presence or history of brain metastases. History of brain metastases History of prior brain metastases Patients who have metastases to the brain. The patient has active brain metastases History of, or current brain metastases Patients must have a history of brain metastases that are non-progressing. Patients with a prior history of brain metastases are eligible provided:\r\n* The brain metastases have been treated\r\n* The patient is asymptomatic from the brain metastases\r\n* Corticosteroids prescribed for the management of brain metastases have been discontinued at least days prior to registration\r\n* The brain metastases are stable on pre-registration imaging Metastases in the brain Subjects with active brain metastases. Untreated brain metastases, symptomatic brain metastases, brain metastases requiring steroids to manage symptoms, or treatment for brain metastases within weeks prior to randomization; Patient does not have any brain metastases in the genu Patients with brain metastases in the genu If history of brain metastases must be stable for at least months after treatment a brain computed tomography (CT) scan or MRI is only be required in subjects with known brain metastases at the time of enrollment or in subjects with clinical signs or symptoms suggestive of brain metastases Presence or history of brain metastases Brain metastases or a history of brain metastases Metastases to brain per prior clinical evaluation; Subjects with brain metastases Greater than brain metastases; excluding previously treated and stable brain metastases Patients with brain metastases. History or evidence of brain metastases Active uncontrolled or symptomatic brain metastases; previously treated and clinically stable, as per investigators judgment, brain metastases are permitted Patient must have or less brain metastases Brain metastases meeting either of the following exclusion criteria:\r\n* Untreated brain metastases\r\n* After completion of brain-directed therapy, the patient has not been able to tolerate discontinuation of steroids or a decrease in steroid dose More than four additional diagnosed brain metastases Patients must have - brain metastases total Current symptomatic brain metastases; if previously present, the metastases must have been treated at least two months before participation in this study; CT or MRI scan of the brain is mandatory to assess the presence or not of brain metastases Presence of brain metastases Patients with symptomatic or progressive brain metastases are ineligible; subjects with treated brain metastases are eligible if they have no radiographic or other signs of progression in the brain for >= weeks after completion of local therapy Patients with untreated brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases; patients with brain metastases that have been definitively treated and on stable or decreasing dose of steroid within weeks of starting study treatment will be eligible Presence of brain metastases History of brain metastases within the last four years Patients with brain metastases (except as allowed in section .. of the protocol. Neurological assessment will be used to determine brain metastases. Patient with active brain metastases are not eligible. Patients with treated brain metastases are eligible if : Either no brain metastases or irradiated stable brain metastases Brain metastases. Note: Patients with a history of brain metastases may be eligible, if an imaging scan with contrast enhancement not older than weeks is able to exclude the existence of currently active brain metastasis Symptomatic brain metastases (if a patient has brain metastases and is on steroids, the steroid dose must have been stable for at least days) or brain metastases that have not been previously treated Documented primary brain malignancy or brain metastases Active brain metastases Patients with brain metastases Patients with known brain metastases should be excluded from this clinical trial; no additional workup is needed to exclude brain metastases if the patient is asymptomatic or has no history of brain metastases Known brain metastases, except brain metastases that have been previously removed or irradiated and currently have no clinical impact If history of brain metastases must be stable for at least months after treatment-a brain computed tomography (CT) scan will only be required in subjects with known brain metastases at the time of enrollment or in subjects with clinical signs or symptoms suggestive of brain metastases Active brain metastases; patients with treated and stable (for at least weeks) brain metastases are eligible; brain metastases will not be considered measurable lesions for the purpose of this trial Primary brain tumors or active brain metastases Patients with brain metastases (including treated or stable brain metastases) Patients must not have active brain metastases from a systemic solid tumor Brain metastases or a history of brain metastases Patients who have had brain metastases will be eligible only if all of the following are true:\r\n* The total number of brain metastases ever is =< \r\n* All are less than or equal to cm\r\n* They have been resected surgically or have been treated with gamma-knife or stereotactic radiosurgery\r\n* The patient has not taken any steroids =< days prior to registration for the purpose of managing their brain metastases All subjects with brain metastases, except those meeting the following criteria: a. Brain metastases have been treated locally, have not been progressing at least months after completion of therapy, and no steroid maintenance therapy is required, and b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) Brain metastases considered unstable as: Brain metastases considered unstable as: Patients must not have history of brain metastases Presence of brain metastases Cancer metastases in the brain History of brain or other CNS metastases. Documented brain metastases Brain metastases: brain metastases must have been treated at least weeks prior to enrollment, be asymptomatic from brain metastases, stable on brain imaging, and not be receiving a supra-physiologic dose of steroids (> mg prednisone daily or equivalent). There is no limit on the number of brain metastases One or more brain metastases Patients who had treatment for their brain metastases greater than month prior to treatment will be eligible; any brain metastases must be stable and not progressing prior to study entry Individuals with symptomatic or progressive brain metastases are ineligible; subjects with treated brain metastases are eligible if they have no radiographic or other signs of progression in the brain for >= weeks after completion of local therapy; any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for >= weeks prior to study enrollment Active brain metastases or unevaluated neurologic symptoms suggestive of brain metastases; subjects with brain metastasis and documented stable disease for > weeks may be included in this study; brain metastases will not be considered measurable lesions for the purposes of this trial History or evidence of brain metastases Documented and ongoing brain metastases Documented brain metastases CNS or Brain metastases Patients with evidence upon physical examination of brain tumor and any brain metastases Active brain metastases No more than brain metastases Uncontrolled brain metastases and infections; patients with brain metastases treated with gamma knife (GK) or whole brain radiation within hours of registration Subjects with brain metastases are excluded if their brain metastases are: Active seizure disorder or evidence of brain metastases; (appropriate imaging should be done to rule out brain metastases) Patients with brain metastases Previously documented or current brain metastases. Brain metastases Patients with stable, treated brain metastases are eligible for this trial. However, patients must not have required steroid treatment for their brain metastases within days of Screening. Brain metastases Active brain metastases. Clinically active brain metastases Patients with known brain metastases should have their brain metastases treated prior to enrollment on this protocol; subjects may enroll on this trial after completion of whole brain radiation therapy and/or stereotactic radiosurgery, provided they are clinically without evidence of progressive brain metastases Subjects with known or suspected brain metastases, primary brain tumors, or brain as the only site of disease Patients must have no clinical evidence of active brain metastasis. Patients with a history of brain metastases must meet all of the following criteria: History or clinical evidence of brain metastases Patients with a prior history of brain metastases are eligible provided:\r\n* The brain metastases have been treated\r\n* The patient is asymptomatic from the brain metastases\r\n* Corticosteroids prescribed for the management of brain metastases have been discontinued at least days prior to registration Presence of symptomatic or uncontrolled brain or central nervous system metastases. Patients with stable, treated brain metastases are eligible for this trial. However, patients must not have required steroid treatment for their brain metastases within days of Screening. Documented primary brain malignancy or brain metastases. Recurrent brain metastases from breast cancer Patients with stable brain metastases are eligible for this trial. However, patients must not have required steroid treatment for their brain metastases within days of Screening. Brain metastases Documented metastases to brain or meninges. Active or progressing brain metastases Patients with known active progressive brain metastases; patients with prior treated brain metastases are allowed, providing that they were not accompanied by seizures within the past year and that a baseline brain MRI scan prior to study entry demonstrates no current evidence of active brain metastases; all patients with prior treated brain metastases must be stable for > months after treatment and off steroid treatment prior to study enrollment Brain metastases that are untreated or symptomatic, or require any radiation, surgery, or steroid therapy to control symptoms from brain metastases within days of first on-study thrombokinetic study; for patients with newly diagnosed brain metastases or unequivocal progression of brain metastases on screening scans, localized treatment (i.e., surgery, radiosurgery, and/or whole brain radiotherapy) is required before study enrollment; subjects with known brain metastases must have clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by days of stable neurologic function prior to the first thrombokinetic procedure; patients with small brain metastases not symptomatic and deemed requiring treatment by managing clinicians or study investigators may be permitted to enroll on study Active or progressing brain metastases Patients with known uncontrolled brain metastases are excluded; however, patients with stable brain disease (off corticosteroids) at least weeks after completion of appropriate therapy for their brain metastases are eligible Active brain metastases Uncontrolled brain metastases Presence of brain metastases Brain metastases with symptoms or requiring treatment Subjects with brain metastases First presentation of brain metastases Subjects may have distant metastasis, including brain metastases. Subjects with known brain metastases are eligible if: Patients with brain metastases are excluded Uncontrolled brain metastases; patients with brain metastases are permitted if they have received appropriate therapy and demonstrated control of the brain metastases following therapy; patients with known brain metastases will require magnetic resonance imaging (MRI) brain to demonstrate disease control prior to enrollment (lack of symptom progression for two weeks off therapeutic doses of steroids, excluding chronic steroids used for control of chronic obstructive pulmonary disease [COPD]) Presence of brain metastases Metastases to the brain Metastases to the brain Participant had breast cancer with brain metastases Metastases to the brain Patients with known brain metastases, history of brain metastases or radiation to the brain. Patients with a prior history of brain metastases are eligible provided:\r\n* The brain metastases have been treated \r\n* The patient is asymptomatic from the brain metastases\r\n* Corticosteroids prescribed for the management of brain metastases have been discontinued at least days prior to registration \r\n* The brain metastases are stable on pre-registration imaging Patients with active CNS or other brain metastases Brain metastases Active or progressing brain metastases Patients with primary brain tumors or primary tumors with central nervous system metastases as only location of disease. Controlled brain metastases are permitted CNS tumor or clinically active brain metastases. Brain metastases have been treated.