Cholestatic disorders or unresolved veno-occlusive disease of the liver. Patients with a history of venous occlusive disease of the liver Participants who have undergone a liver transplant or those who are in the waiting list for liver transplantation Cirrhotic liver disease from any cause Hepatic metastases on imaging meeting the following criteria:\r\n* Liver-only or liver-dominant metastases, defined as:\r\n** At least % liver parenchyma replacement by tumor, but less than % replacement of the hepatic parenchyma by tumor\r\n*** For the imaging sub-study: at least one liver lesion must measure greater than cm in size\r\n*** For the imaging sub-study: treatment must only be performed using a single dose, and so arterial variant anatomy that would result in a split treatment will not be allowed\r\n** And, progression of the liver metastases demonstrated within the past twelve months defined as either:\r\n*** Appearance of any new liver lesion or\r\n*** % increase in size of at least one liver lesion\r\n** Presence of low-volume extrahepatic lesions (including primary tumor) is allowed if they are asymptomatic\r\n* SUVmax on Ga-DOTA-TOC PET of the liver metastases two times greater than the adjacent liver parenchyma Greater than % tumor burden in the liver by imaging. Has metastatic liver involvement that does not exceed / of the total liver volume in participants to be treated by liver IT injection. Hepatocellular carcinoma participants are excluded from eligibility of IT liver injection. No prior local, liver-directed therapy; prior surgical resection of oligometastatic liver disease is allowed History of cirrhotic liver disease Known history of chronic liver disease Participant has a history of liver disease Prior radioembolization to the liver Chronic liver disease Have pre-existing alcoholic liver injury or significant liver disease. High screening liver function tests Presence of parenchymal liver metastases on imaging Patients with recent (within days preoperatively) history severe hepatic disease (defined as liver injury with encephalopathy plus impaired synthetic liver function (i.e. > .). Patients who have been previously treated with non-SBRT liver directed therapies (with the exception of intrahepatic Y infusion) may be enrolled on study; at least months must have elapsed between the most recent liver-directed therapy and study entry Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone e.g., presence of active GVHD of the liver as manifested by rising liver function tests (LFTs) prior to initiation of study treatment Uncontrolled adrenal insufficiency or active chronic liver disease Liver metastases with no other metastatic sites Participants must have biopsy-proven diagnosis of a colorectal cancer with - liver metastases; there is no upper size limit and participants must have at least mL of uninvolved liver; liver metastases may be diagnosed by imaging alone, no liver biopsy is required; extrahepatic disease is allowed if ) it has been stable for months prior to study entry, ) the dominant disease burden is intrahepatic and ) the patient is referred for definitive radiation therapy to the disease in the liver Participants must have liver metastases deemed unresectable due to anatomy, medical fitness, or presence of extrahepatic disease Childs class C liver disease or worse No history of severe prior or ongoing chronic liver disease History of cirrhotic liver disease Patients with greater than % liver tumor burden Abnormal liver function tests (LFTs) in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the LFTs as being consistent with hepatic cGVHD and a liver biopsy will not be mandated in this situation Patients must have liver-only metastases or predominant liver metastatic disease Liver involvement by > % with metastatic disease determined by the investigator Known liver disease Subjects with diagnosed active liver disease or with elevation of liver enzymes/bilirubin. Patients must have liver metastasis Patients with a history of prior irradiation or other treatment to the liver or abdomen who after treatment on this protocol would have a cumulative dose to the liver or other normal tissues greater than the protocol defined constraints Uncontrolled adrenal insufficiency or active chronic liver disease Active hepatitis B or C infection with abnormal liver functions (i.e., liver function tests [LFTs] > X upper normal limits) Patients must have histologically or cytologically confirmed colorectal cancer with liver metastases deemed resectable by a general or liver surgeon (resectability may involve the use of ablative techniques to some but not all liver metastases); those patients with known disease outside of the liver are not eligible (except for patients with primary lesions in place that are planned for resection or nonspecific lung metastases < cm) Patients with synchronous or metachronous diagnosis of resectable liver metastases by computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen: a) patients requiring percutaneous or intraoperative ablation of liver metastases < cm in size are eligible; b) patients who underwent prior liver resection or ablation for colorectal liver metastases are eligible Compromised liver function as defined by any of the following:\r\n* Cohort : Advanced cirrhosis group\r\n** Borderline Child-Pugh class A\r\n** Child-Pugh class B\r\n*** The patients in this advanced cirrhosis group must have at least ml of functional liver, as estimated on either diagnostic imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) or single photon emission computed tomography (SPECT)/CT with Tc-m sulfur colloid; there is no upper limit on the functional liver volume for these patients\r\n* Cohort : Low functional liver volume without underlying chronic liver disease\r\n** Previous irinotecan or oxaliplatin chemotherapy\r\n** Previous liver resection(s)\r\n*** These patients must have at least ml of functional liver, as estimated by either diagnostic imaging computed tomography or magnetic resonance imaging (CT or MRI) or SPECT/CT with Tc-m sulfur colloid\r\n* Cohort : History of prior liver-directed radiation therapy with either fractionated external beam radiation therapy (EBRT), stereotactic body radiation therapy (SBRT) or yttrium- radioembolization (Y RE); the interval between prior EBRT and re-irradiation on protocol should be equal to or greater than months; the interval between prior Y RE and re-irradiation on protocol should be equal to or greater than months; \r\n** Cirrhosis group:\r\n*** Child-Pugh class A; \r\n*** Borderline Child-Pugh class A; \r\n*** The patients in this group must have at least ml of functional liver, as estimated on either diagnostic imaging (CT or MRI) or SPECT/CT with Tc-m sulfur colloid; there is no upper limit on the functional liver volume for these patients\r\n*Low functional liver volume without underlying liver disease\r\n** Previous irinotecan or oxaliplatin chemotherapy\r\n** Previous liver resection(s)\r\n** These patients must have at least ml of functional liver, as estimated by either diagnostic imaging (CT or MRI) or SPECT/CT with Tc-m sulfur colloid; there is no upper limit on the functional liver volume for these patients Metastatic disease outside of the liver In patients with liver metastases, there should be < % involvement of the liver Liver tumors must not be estimated to invade approximately more than one-third of the liver. Patients with parenchymal liver metastases. At least one thoracic or liver lesion amenable to radiation, for group we need one area that can safely receive SBRT or WFRT, not restricted to lung or liver sites Liver function tests > x upper limit of normal Bilirubin < . x normal except in cases where abnormal liver function tests (LFTS) are due to involvement with T-NHL Known or active hepatitis B or C with abnormal liver function tests Liver function test (LFTs) =< x upper limit of normal Tumor involving > % of the liver Patients with a history of or active liver failure Liver enzymes < fold the upper limit of normal Scans used to determine eligibility (CT scan of the chest/abdomen/pelvis and MRI of the liver) must be performed within days prior to randomization. An MRI of the liver is required at screening to validate that CT accurately reflects the extent of disease in the liver. For patients with MRI intolerance, a -phase liver CT is to be done in place of liver MRI. Extensive liver tumor burden, defined as more than % of the liver Histologically confirmed diagnosis of cancer with liver metastases, or histologically confirmed primary liver cancer (e.g. hepatocellular carcinoma, cholangiocarcinoma, or gallbladder carcinoma); subjects may have extrahepatic spread of malignancy, except they may not have brain metastases; subjects with a history of more than one invasive malignancy remain eligible for this study, but in these instances, a liver biopsy is required to document the histology of the liver tumor; an exception to this criterion is made for basal cell carcinoma Prior liver resection of greater than anatomic segments as defined by Couinaud; (subjects that have undergone prior liver wedge excisions or segmental resections are not excluded on this basis alone) No history of severe prior or ongoing chronic liver disease Loco-regional therapy to the liver within days before randomization History of chronic liver disease. History of chronic liver disease. Chronic inflammatory liver condition. History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver) Liver tumors must not be estimated to invade approximately more than one-third of the liver. Chronic liver dysfunction prior to development of liver metastases (Child-Pugh C or greater). Severe liver disease Severe liver disease Uncontrolled adrenal insufficiency or active chronic liver disease Liver function tests performed within weeks prior to starting study therapy must have albumin >= . g/dL Liver function tests > x upper limit of normal History or current evidence of malabsorption or liver disease that would impair the absorption of itraconazole ARM A: Disease burden in liver not affecting more than % of liver ARM A: Predominant intrahepatic burden (> %) of disease (i.e. patients with widespread extrahepatic disease to organs other than the liver will not be included) ARM B: Disease burden in liver not affecting more than % of liver Total bilirubin =< . x ULN; unless presence of Gilbert's syndrome, liver involvement by CLL or MM, or stable chronic liver disease per investigator's assessment Liver disease, except Gilbert's syndrome, liver involvement by CLL or MM, or stable chronic liver disease per investigator's assessment Decompensated liver disease in which pegylated interferon is contraindicated History or other evidence of decompensated liver disease History or other evidence of decompensated liver disease Liver disease. Ongoing liver injury Abnormal liver function test results Liver function tests (LFTs) greater than twice the upper limit of normal Cancer that has spread to the liver or brain Subjects with known history, or clinical or laboratory evidence of liver disease Patients must have liver metastases. History of current evidence of malabsorption or liver disease Suspected pulmonary and/or liver metastases (greater >= mm in largest axis) Any of the following liver findings: ALT >.xULN, ALT > xULN with liver metastases/tumor infiltration, Bilirubin >.xULN (isolated bilirubin >.xULN is acceptable if bilirubin is fractionated and direct bilirubin <%), Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment). NOTE: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice or cirrhosis Has clearly resectable colon cancer liver metastases (CCLM), for example oligometastatic disease involving only one lobe of the liver. Subjects with suspected resectable CCLM should undergo evaluation by a liver surgeon prior to enrollment to document the incurable nature of their disease. For patients with abnormal liver function tests (LFTs) as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situation For participants with abnormal liver function tests (LFTs) as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situation History of chronic liver disease. History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver) Liver metastases Prior liver directed therapies will be permitted (i.e. chemoembolization, radioembolization) as long as target lesions in the liver have demonstrated growth since the liver directed treatment Prior peptide receptor radionuclide therapy (PRRT) will be permitted as long as target lesions in the liver have demonstrated growth since the liver directed treatment Abnormal liver function tests (bilirubin more than .xULRR, and ALT, AST, or ALP more than .xULRR or .xULRR if related to liver metastases). Known hepatitis B virus carriers who have liver function tests within the accepted limits are eligible LIVER (ONLY APPLIES TO PATIENTS WITH METASTATIC LIVER LESIONS NOT PREVIOUSLY TREATED WITH RT): History of serious liver disease Chronic or active hepatitis B or hepatitis C; if questions about liver health, discuss with principal investigator (PI) and strongly consider liver biopsy Acute liver disease or previously diagnosed liver tumor (benign or malignant) Subjects with unresolved veno-occlusive disease of the liver. Preserved liver function Presence of advanced liver disease. Ongoing liver injury History of chronic liver disease. Patients must have liver-only or liver-predominant disease to be eligible for this study; liver predominant disease is defined dominant metastatic burden in the liver, with extra-hepatic disease that is judged by the investigator as unlikely to be life threatening within months Patients with previous chemoembolization to liver metastases Ongoing liver injury Patients with liver metastases that replace greater than % of the liver parenchyma Significant liver disease or metastatic disease to the liver Patients with abnormal liver function will be eligible and will be grouped according to the criteria described; patients with active hemolysis should be excluded; no distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causes History of cirrhotic liver disease Patients with > liver metastases at time of enrollment Patients must have one focus of metastatic disease in the liver that is amenable to SBRT in the opinion of radiation oncology Prior liver directed radiation Liver function tests (LFTs) > x nl Patients should have hepatic function (alkaline phosphatase, AST and ALT) < ULN and renal functions with serum creatinine - <. x UNL. If a patient has liver metastasis and/or a history of liver disease - they will receive a lower dose of the drug per treatment protocol. Patients with known liver metastases History of chronic liver disease. History of chronic liver disease Patients with known liver disease Underlying chronic liver disease with evidence of severe liver impairment. History or current hepatitis or other liver disease History or current evidence of malabsorption or liver disease that would impair the absorption of Itraconazole as measured by liver function tests within the past one year prior to enrollment Normal liver function based on Liver Function Tests (Total Bilirubin and AST <. X Upper Limit of Normal). Metastatic disease outside of liver Greater than % tumor burden in the liver by imaging Liver function tests with values > x ULN Liver metastases History of veno-occlusive disease of the liver Patients with history of severe liver disease, defined as and confirmed by albumin less than . History of liver disease Potential subjects will be excluded for a number of medical conditions that might represent a risk for riluzole (including history of allergic reaction to riluzole and evidence of liver disease) and potentially confound the relationship among CNS glutamate, inflammation and behavior/cognition, including: autoimmune or inflammatory disorders, chronic infectious diseases (e.g. human immunodeficiency virus [HIV], hepatitis B or C), pregnancy, neurologic disorders (including a history of serious head trauma or seizures), liver disease (as manifested as an elevation in liver transaminases), uncontrolled cardiovascular, metabolic, pulmonary or renal disease (as determined by medical history and laboratory testing) Chronic liver disease Liver tumor burden less than or equal to % Patients undergoing open elective liver resection for primary liver pathology (benign or malignant) or secondary metastatic liver disease, including patients undergoing concomitant surgical procedures (such as colorectal resection or debulking procedures), with no contraindication to the insertion of an epidural catheter (localized infection, septicemia, or pre-operative coagulopathy) Significant liver disease that would inhibit prescription of opioids Patients must have liver tumors requiring a major liver resection, defined as removing at least three anatomical segments in patients without liver disease and two segments in patients with cirrhosis/fibrosis of the liver No liver failure Chronic liver disease or in participants without known liver disease, alanine aminotransferase (ALT) >= x normal Total bilirubin < . mg/dl; unless hepatic dysfunction is a manifestation of presumed cGVHD; for patients with abnormal liver function tests (LFTs) as the sole manifestation of active cGVHD, documented cGVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with active hepatic cGVHD, and a liver biopsy will not be mandated in this situation For participants with abnormal liver function tests (LFTs) as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situation No significant synthetic dysfunction of the liver; if there is a question of such, a liver biopsy should be performed for further assessment History of hepatitis or liver disease Diffuse intrahepatic metastases that involves > % of the liver For patients with abnormal liver function tests (LFTs) above the thresholds, documented cGVHD on liver biopsy will be required prior to enrollment Able to undergo:\r\n* Percutaneous or transjugular biopsy of cirrhotic liver at least days prior to liver resection (surgical cohort), OR\r\n* A biopsy of the cirrhotic liver (non-surgical cohort) Willingness to authorize collection of tissue from surgically-resected liver or clinical liver biopsy for analyses Patients with end stage liver disease or anticipated liver transplant within the next two years will be excluded; a history of liver transplant is not an exclusion per se, if patient does not meet stated hepatic criteria Individuals with history of liver disease in last months Liver metastases on most recent prior M.D. Anderson CT examination. Patients with liver failure are NOT eligible. History of liver disease within the last months Patients with confined liver disease or stable limited extrahepatic disease Liver function tests (LFTS) =< . x upper limit of normal (ULN) Patients must have liver-dominant or liver-only metastatic disease from any primary histology; patients with primary hepatocellular or biliary cancer are also eligible Patients not undergoing radioembolization to the liver History of having undergone any local ablative therapy to liver prior to enrollment on the trial Prior systemic treatment or radiation therapy is allowed for patients with resectable liver metastases\r\n* The last dose of chemotherapy or radiation must have been administered at least weeks prior to liver surgery\r\n* The last dose of bevacizumab must have been administered at least weeks prior to liver resection History of liver disease as defined with liver function tests (LFTs) above those in the inclusion Criteria , More than one third of the liver is estimated to be involved with metastases